A Simulation Study on Controlling Ultrasound Resonances in Multi-well Microplates

Sammanfattning

Three-dimensional (3D) cell cultures are important in constructing tumor microenvironments for anti-cancer drug development. Ultrasound standing waves (USWs) enable non-invasive manipulations of cells and form 3D cultures on microscopy-compatible chips. However, at a single resonance frequency, USWs create diagonal potential wells, resulting in non-spherical cell clusters. Frequency sweeping centralizes spheroids but lowers energy efficiency due to off-resonant frequencies. This project aims to improve the performance and efficiency of USW-driven multi-well microplates (chips) by simulating devices using COMSOL Multiphysics. Two model types were developed: eigenfrequency models to explore intrinsic resonance patterns, and piezo-driven models coupling actuators to the chips. Eigenfrequency models revealed symmetric resonance patterns (C_2 and C_4 symmetries identified) that can be exploited to improve spheroid centralization with less energy loss. Piezo-driven models highlighted how coupling methods, such as glue layer thickness, impact conductance and energy loss, and identified a levitation effect that may prevent cells from adhering to well walls. Additionally, alternating power supply on piezo terminals yielded the most uniform energy distribution across wells. Results from this study improve device performance and provide practical insights to optimize designs and actuation methods, contributing to the future development of microscopy-compatible, ready-to-use 3D cell culture chips.